1. ¹Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan
2. ²Department of Radiation Oncology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan
3. ³Department of Radiation Oncology, UCLA, CA, USA

Correspondence: Dr C-S Chiang, Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University; 101 Sec 2, Kuang-Fu Road, Hsinchu 30013, Taiwan, Taiwan. E-mail: cschiang@mx.nthu.edu.tw

Received 1 February 2006; Revised 1 April 2006; Accepted 14 May 2006; Published online 14 July 2006.

Abstract

The aim of this study was to investigate means of increasing the efficiency with which cancer cell death following local radiation therapy (RT) is translated into the generation of tumor immunity since, if this were to be achieved, it would be expected to enhance the rates of disease-free recurrence and survival. Our investigations centered around the use of interleukin-3 (IL-3), expressed intratumorally using an inducible adenoviral vector, to alter the immunogenicity of established murine TRAMP-C1 prostate cancer receiving a course of fractionated local RT (7 Gy per fraction per day for 5 days). Because high systemic levels of IL-3 can be associated with toxicity, a tetracycline-regulated gene delivery system was employed. The results show that while intratumoral IL-3 expression or RT alone caused a modest delay in TRAMP-C1 tumor growth, the combination was synergistic with 50% of mice being cured and developing a long-term, tumor-specific state of immunity. Immunological analyses performed on splenic lymphocytes demonstrated that, compared to RT or IL-3 alone, combined treatment significantly increased the number of tumor-specific IFN--secreting and cytotoxic T cells. The study demonstrates that tetracycline-regulated IL-3 gene expression within tumors can enhance the immune response to prostate cancer and this can augment the efficacy of a course of RT without additional side effects.